Portable, nitric oxide generator

ABSTRACT

An apparatus for portable delivery of nitric oxide without the need for pressurized tanks, power supplies, or other devices provides a single therapy session by triggering a heater to heat a reaction chamber. A piercing assembly may trigger to open sealed containers, such as bags, of liquid water or salt water in order to activate the heaters. Upon addition of liquid such as water or salt water to a chemically reactive heating element, heat is generated to activate the chemicals generating nitric oxide within a sealed reactor. Upon triggering, liquid containers are unsealed, the liquid drains down to initiate reaction of the heating chemicals, and the heat begins to penetrate the reactor. The reactor, in turn, heats its contents, which react to form nitric oxide expelled by the reactor to a line feeding a cannula for therapy.

RELATED APPLICATIONS

This patent application claims the benefit of co-pending U.S.Provisional Patent Application Ser. No. 61/043,064 filed Apr. 7, 2008,which is incorporated herein by reference. This patent application isalso a continuation-in-part of co-pending U.S. patent application Ser.No. 11/751,523 filed May 21, 2007, which is incorporated herein byreference, which is a continuation-in-part of U.S. patent applicationSer. No. 10/733,805 filed Dec. 10, 2003, which is incorporated herein byreference, which claims the benefit of Canadian Patent Application No.2413834, filed Dec. 10, 2002.

BACKGROUND

1. The Field of the Invention

This invention relates generally to chemical reactors, and morespecifically to apparatus and methods for generating nitric oxide.

2. Background

The discovery of certain nitric oxide effects in live tissue garnered aNobel prize. Much of the work in determining the mechanisms forimplementing and the effects of nitric oxide administration are reportedin literature. In its application however, introduction of bottlednitric oxide to the human body has traditionally been extremelyexpensive. The therapies, compositions, and preparations aresufficiently expensive to inhibit more widespread use of such therapies.What is needed is a comparatively inexpensive mechanism for introducingnitric oxide in a single dosage over a predetermined period of time.Also, what is needed is a simple introduction method for providingnitric oxide suitable for inhaling.

It would be an advance in the art to provide a single dose generatorsuitable for administration of nitric oxide gas. It would be an advancein the art to provide not only an independence from bottled gas, butfrom the need for a source of power for heat, or the like. It would be afurther advance in the art to provide a disposable generator to beinitiated by a trigger mechanism and operate without furthersupervision, adjustment, management, or the like. Likewise, it would bea substantial benefit to provide a system that requires a minimum ofknowledge or understanding of the system, which might still be safe foran individual user to administer with or without professionalsupervision.

BRIEF SUMMARY OF THE INVENTION

In accordance with the foregoing, certain embodiments of an apparatusand method in accordance with the invention provide a self-containedreactor system. Nitric oxide may thus be introduced into the breathingair of a subject. Nitric oxide amounts may be engineered to deliver atherapeutically effective amount on the order of a comparatively lowhundreds of parts per million, or in thousands of parts per million. Forexample, sufficient nitric oxide may be presented through nasalinhalation to provide approximately five thousand parts per million inbreathing air. This may be diluted due to additional bypass breathingthrough nasal inhalation or through oral inhalation.

One embodiment of an apparatus and method in accordance with the presentinvention may rely on a small reactor. Reactive solids may beappropriately combined dry. Reactants may include potassium nitrite,sodium nitrite or the like. The reaction may begin upon introduction ofa heat. Heat may be initiated by liquid transport material to supportionic or other chemical reaction in a heat device.

An apparatus and method in accordance with the invention may include aninsulating structure, shaped in a convenient configuration such as arectangular box, a cylindrical container, or the like. The insulatingcontainer may be sealed either inside or out with a containment vesselto prevent leakage of liquids therefrom. Such a system need not beconstructed to sustain nor contain pressure. Inside the containmentvessel may be positioned heating elements such as those commerciallyavailable as chemical heaters.

In certain embodiments, chemical heaters may include metals finelydivided to readily react with oxygen or solid oxidizers. Various otherchemical compositions of modest reactivity may be used to generate heatreadily without the need for a flame, electrical power, or the like.

Above the heating element or heater within the containment vessel may belocated a reactor. The reactor may preferably contain a chemicallystable composition for generating nitric oxide. Such compositions, alongwith their formulation techniques, shapes, processes, and the like aredisclosed in U.S. patent application Ser. No. 11/751,523 and U.S. Pat.No. 7,220,393, both incorporated herein by reference in their entiretiesas to all that they teach.

The reactor may include any composition suitable for generating nitricoxide by the activation available from heat. The reactor may besubstantially sealed except for an outlet, such as a tubular membersecured thereto to seal a path for exit of nitric oxide from thereactor.

In certain embodiments, a system of water or salt water may be availablein the container. In one embodiment, the water containers may be assimple as presealed bags, such as polyethylene bags that can be opened,cut, torn, or otherwise pierced in order to release water therefrom.Accordingly, a system may include a heating element or the reactor, sucha water source to provide a chemical transport fluid, a piercingassembly for the water containers, a trigger for activating the piercingassembly, and blades, hooks, cutters, punches, or the like structured toopen the bags containing water.

Upon triggering of the piercing assembly, the water is released from thewater containers, vessels, bags, or the like, to be poured down throughthe assembly onto the heating elements where heaters are activated bythe presence of a liquid. It has been found through experiments thatadding the additional ionic content of salt improves the reaction rateof chemical heating systems.

Ultimately, an apparatus in accordance with the invention may include acover through which an outlet penetrates from the reactor in order toconnect to a cannula. This has been done effectively. It will alsosupport a vent for steam generated by the heaters in the presence of thewater used to activate the heaters. The system may be completely wrappedin a pre-packaged assembly. In one embodiment, a heat-shrinkablewrapping material may be used to seal the outer container of anapparatus in accordance with the invention. Thus, this system may berendered tamper proof, while also being maintained in integral conditionthroughout its distribution, storage, and use.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing features of the present invention will become more fullyapparent from the following description and appended claims, taken inconjunction with the accompanying drawings. Understanding that thesedrawings depict only typical embodiments of the invention and are,therefore, not to be considered limiting of its scope, the inventionwill be described with additional specificity and detail through use ofthe accompanying drawings in which:

FIG. 1 is a perspective view of one embodiment of an apparatus inaccordance with the invention to generate nitric oxide from a chemicallyactive source of nitric oxide, as a result of exposure to heat;

FIG. 2 is an exploded view of the apparatus of FIG. 1 for generatingnitric oxide;

FIG. 3 is a top plan view of an insulating container for the apparatusof FIG. 1;

FIG. 4 is a side elevation view of the box-like container of FIG. 3;

FIG. 5 is an end, elevation, cross-sectional view of the container (box)of FIGS. 3-4;

FIG. 6 is a top plan view of a cover for the container of FIGS. 3-5;

FIG. 7 is an end elevation view of the cover of FIG. 6;

FIG. 8 is a side elevation view of the cover of FIG. 6;

FIG. 9 is a side elevation view of a vent for the portable nitric oxidedevice of FIG. 1;

FIG. 10 is a top plan view of the vent illustrated in FIG. 9;

FIG. 11 is a front elevation view of a triggering pin for the apparatusof FIG. 1;

FIG. 12 a is an end view of the pin of FIG. 11;

FIG. 12 b is a side elevation view of the pin of FIG. 11;

FIG. 13 is a bottom plan view of a guiding rod for holding a compressionspring used in the trigger device of the apparatus of FIG. 2;

FIG. 14 is a side elevation view of the guide rod of FIG. 13;

FIG. 15 is a front elevation view of a spacer used in the piercingassembly of FIG. 2;

FIG. 16 is a top plan view of the spacer of FIG. 15;

FIG. 17 is a top plan view of the mounting assembly for a blade of thepiercing assembly of the apparatus of FIG. 2;

FIG. 18 is an end elevation view of the mounting assembly or carrier forblades in the piercing assembly of FIG. 2, and corresponds to theapparatus of FIG. 17;

FIG. 19 is a side elevation view of the mounting assembly with blades inplace, and corresponds to the apparatus illustrated in FIGS. 17-18;

FIG. 20 is a side elevation view of a base or base plate for supportingthe blades in the piercing assembly of the apparatus of FIG. 2;

FIG. 21 is a top plan view of the base or base plate of the apparatus ofFIG. 20;

FIG. 22 is a side elevation view of a cover plate for the blades in thepiercing assembly of the apparatus of FIG. 2;

FIG. 23 is a top plan view of the cover plate of FIG. 22;

FIG. 24 is a side elevation view of a spring, used as a compressionspring to drive the mounting assembly of FIG. 17, with the bladesinstalled to operate the piercing assembly of FIG. 2;

FIG. 25 is a top plan view of one embodiment of a containment vesseloperating as a reactor for the nitric oxide generation from the chemicalspecies contained therein;

FIG. 26 is a side elevation view of the reactor's containment vessel ofFIG. 25;

FIG. 27 is a side elevation view of one embodiment of a tube configuredto operate as an outlet for the reactor vessel of FIG. 25;

FIG. 28 is a perspective view of one embodiment of a shrink-wrap sleevethat is applied to contain the overall enclosure of the apparatus ofFIGS. 1-2;

FIG. 29 is a perspective view of the apparatus of FIGS. 1-2;

FIG. 30 is a top view of the apparatus of FIG. 29 open for viewing ofthe internal apparatus;

FIG. 31 is a top view of the assembled apparatus of FIGS. 1-30 with thewater containers removed to place the piercing assembly in view;

FIG. 32 is a perspective view of the assembled blades, spring, mountingassembly, cover plate and base plate of the piercing assembly of FIGS. 2and 31;

FIG. 33 is another perspective view of the insulating container orcontainment box, reactor, and outlet for the reactor, along with thepiercing assembly displaced, for better viewing of the reactor, and alsofor providing an improved view of certain details of the piercingassembly;

FIG. 34 is a graph showing data for the temperature rise in degreesFahrenheit of the reactor of FIGS. 2, 25, 26, 32, and 33 using a varietyof heaters including a single heater relying on water as the liquid, twostandard heaters relying on water, and a single heater using salt wateras the activating liquid;

FIG. 35 is a graph depicting the temperature response of the reactor ofFIGS. 1-33 over time in both a single heater and double heaterconfiguration;

FIG. 36 is a graph depicting the temperature response of the reactor ofFIGS. 1-33 as a function of time when heated by a single heater and bydouble heaters; and

FIG. 37 is a chart depicting the released volume of nitric oxide fromthe reactor of FIGS. 1-33 superimposed over the temperature responsethereof as a function of time.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

It will be readily understood that the components of the presentinvention, as generally described and illustrated in the drawingsherein, could be arranged and designed in a wide variety of differentconfigurations. Thus, the following more detailed description of theembodiments of the system and method of the present invention, asrepresented in the drawings, is not intended to limit the scope of theinvention, as claimed, but is merely representative of variousembodiments of the invention. The illustrated embodiments of theinvention will be best understood by reference to the drawings, whereinlike parts are designated by like numerals throughout.

Referring to FIG. 1, an apparatus 10 may be configured as a portablenitric oxide device. In the illustrated embodiment, a container 12 orvessel 12 may provide insulation, liquid sealing, or both. Meanwhile, afitting 14 or outlet 14 may be connected to feed nitric oxide to a line15 proceeding toward a user, for distribution by a cannula, mask, tent,or the like.

In the illustrated embodiment, a trigger 16 or actuator 16 may bewithdrawn from the apparatus 10 in order to trigger the initiation of areaction generating nitric oxide. In certain embodiments, generation ofnitric oxide may depend on temperature of reactants. The generation ofheat (e.g., temperature) may rely on a reaction requiring moisture,which moisture may eventually be partially converted to steam needing tobe vented. Accordingly, a vent 18 may vent the interior of the container12 in order to avoid any buildup of pressure; in one embodiment, theentire container 12 may be sealed in a heat-shrinkable sleeve thatmaintains the integrity of the apparatus 10 during distribution,storage, and use.

Referring to FIG. 2, an exploded view of the apparatus of FIG. 1illustrates one embodiment of the apparatus 10 in accordance with theinvention. In the illustrated embodiment, the outlet 19, connected tofeed through the fitting 14 and thus feed nitric oxide through the line15 may be securely sealed to a reactor 20. The reactor 20 may be formedby any of several suitable methods to contain the chemical constituentsrequired to generate nitric oxide. A port 21 or aperture 21 may beformed to seal against the outlet 19 in order to discharge all of thegenerated nitric oxide to a location outside the apparatus 10.

Below or around the reactor 20 may be located one or more heaters 22 orheating elements 22. In the illustrated embodiment, the heaters 22 areformed to contain solid reactants in a non-woven fabric container. Thereactants are stabilized by being completely dry. In the presence ofliquid, ionic exchange promotes the reaction of the contained chemicalswithin the heaters 22.

In order to contain any liquid to activate the heaters 22, a containmentvessel 24 may surround the heaters 22, within the insulation container26 or box 26. In certain embodiments, the functionality of thecontainment vessel 24 and the insulated container 26 may be consolidatedinto a single structure. Likewise, in certain embodiments, thecontainment vessel 24 may actually be located external to the insulatedcontainer 26.

In general, a liquid, and particularly a hydrating liquid such as water,salt water, or the like, may serve as an activation material. In theillustrated embodiment, the bags 28 containing salt water, water, or thelike may be sealed for storage. In certain embodiments, the containers28 may be capped, vented, or otherwise made resealable. However, inother embodiments, a fully disposable apparatus 10 may rely oninexpensive materials such as polyethylene film to form the containers28.

By any means, an opening assembly 30 (in the illustrated embodiment, apiercing assembly 30) may be actuated to open, pierce, or otherwisebreach the sealing of the containers 28 of liquid. Upon piercing orotherwise breaching of the integrity of the containers 28, the containedliquid then flows downward to be absorbed within the covering materialof the heaters 22. The presence of the liquid activates the chemicalreactions within the heaters 22, generating heat to initiate reaction ofthe chemical constituents contained within the reactor 20.

A cover 32 may enclose the insulated container 26, and may typically beformed of the same material. A vent 30 may vent steam from within thecontainment vessel 24 and the insulated container 26 in order toalleviate any pressure build up. Likewise, in order to direct theresidual steam in a specific direction other than permitting it toescape about the interface between the cover 32 and the container 26, avent 18 may be advisable, required, or otherwise useful.

The outlet 19 for nitric oxide may penetrate through the cover 32 bymeans of an aperture 34. The aperture 34 may be sealed against theoutlet 19 in order that the steam generated from the heaters 22 escapesubstantially exclusively through the vent 18, rather than near thefitting 14 and line 15 that may be subject to manipulation by the user.

Referring to FIGS. 3-37, the insulated container 26 may be formed in anysuitable shape to contain all of the elements required for a singledosing of nitric oxide. Accordingly, the constituent structures of FIG.2 may fit within the interior of the container 26. Meanwhile, the cover32 may be fitted thereto.

The vent 18 may be formed to fit snugly through a penetration in thecover 32. A flange thereof may be labeled with colors and textappropriate to warn of the elevated temperature thereof as a safetymeasure.

A pin may act as a significant portion of the trigger assembly 16 ortrigger 16. Upon removal of the pin, such as by a user pulling on ahandle or ring secured thereto, the blades may be released to pierce thecontainers 28 holding the liquid required to initiate the reaction ofheaters 22.

A guide 36 or guide rod 36 may direct the blades of the piercingassembly 30. A compression spring wrapped around the guide 36 or rod 36may push the blades forward. Referring to FIGS. 13-23, generally, whilespecifically referring to FIGS. 15-16, the piercing assembly 30 may beconfigured to protect against inadvertent exposure to sharp instruments.A spacer 38 may provide room for operation of a blade assembly 39 ormount 39 holding blades 40 secured thereto.

For example, a “T”-shaped mounting assembly may secure two blades 40 a,40 b that will eventually slide parallel to the base of the T, and alongthe same direction of the guide 35 or guide rod 36. In the illustratedembodiment, an aperture in the foot of the T-shaped mount may run alongthe guide rod 36, driven by the compression spring acting along thelength of the rod 36.

The blade assembly or mount 39, together with its attached blades 40 mayoperate by sliding along an upper surface of the baseplate 42. Twoapertures on opposing sides or near opposing edges of the baseplate 42may receive fasteners to penetrate a pair of corresponding spacers 38.The spacers 38 form a clearance above the baseplate 42 for operation ofthe mount 39.

A cover 44 or cover plate 44 may include a pair of apertures at or nearopposing edges thereof to receive the same fasteners that penetrate thebaseplate 42. Accordingly, the cover plate 44, or simply cover 44, isspaced away from the baseplate 42 sufficient distance to receive themount 39 and attached blades 40 therewithin. Thus, the blade assembly 39or mount 39 with its attached blades 40 is effectively “garaged” betweenthe baseplate 42, and the cover plate 44. Meanwhile, a compressionspring 46 pushes against the base of the T-shaped mount 39, driving theaperture therein along the guide rod 36 captured in the aperture.

A reactor 20 may include a principal containment vessel 50. In oneembodiment, a conventional “tin,” or metal can, may be formed byconventional technology available for canning. In other embodiments, thereactor 20 may rely on other structures such as fiber-reinforcedcomposites, cylinders, sealed and flexible but inextensible latticework, fabrics, or the like, in order to contain the chemicalconstituents reacting to form nitric oxide.

In one embodiment, tablets, granules, or other configurations ofreactants may be placed in a can, sealed to form the reactor vessel 50.An aperture 40 in the vessel 50 may receive a tube 52 acting as areactor outlet 19. The outlet 19 may conduct nitric oxide generatedwithin the containment vessel 50 to a location outside the insulatedcontainer 26 in order to deliver to a line 15.

Various mechanisms may be available for maintaining the integrity of theapparatus 10. In one embodiment, a heat shrinkable wrapping material maybe formed in a seamless sleeve. The sleeve may be placed around theapparatus 10, and judiciously penetrated to accommodate the fitting 14,the vent 18, the trigger 16, and so forth. Thereupon, the sleeve 54 maybe heated in order to shrink it snugly about the insulated container 26.Thereafter, any breach of the sleeve 54 indicates a lack of integrity ofthe apparatus 10.

One embodiment of an apparatus 10 in accordance with the invention wasformed using expanded polystyrene for the insulated container 26. Afitting 14 to receive a line 15 delivering nitric oxide to a cannula 56received nitric oxide from a reactor 20 within the insulated container26. A vent 18 penetrated the cover 32 of the insulated container 26 tovent steam. A trigger mechanism 16 penetrated the cover 32 in order toreach the piercing assembly 30 described hereinabove.

Containers 28 filled with salt water were provided and placed above thepiercing assembly 30 and the reactor 20 therebelow. The heaters 22 wereplaced entirely below the reactor 20, although they may also be wrappedtherearound, or even placed on top. However, inasmuch as the heaters 22tend to vaporize some of the liquid in the containers 28 when released,the heated steam generated below the reactor was effective to heat thereactor 20. Steam rising from heaters thereabove would not ever be incontact with the heaters 22. That is, heat rising with steam originatingabove the reactor 20, will not contribute as much heat to the reactor20. The outlet 14 from the reactor was formed of a stainless steel tube52 penetrating the reactor 20.

The blades 40 were positioned between the baseplate 42, and the coverplate 44. The guide rod 36 was secured to the baseplate 42 to maintainalignment of the mount 39 as the spring 46 drove the mount 39 forwardalong the guide rod 36. Upon release of a trigger 16, the mount 39advanced out from under the cover plate 44, exposing the containers 28to the sharp blades 40. The blades 40 compromised the containers 28 frombelow, thus substantially evacuating all the water therefrom. In theexperiment illustrated, salt water was used as the liquid within thecontainers 28. In some experiments, a single container was used. Inother embodiments, including experiments conducted, multiple containers28 filled with liquid were used.

Referring to FIG. 34, in one set of experiments, a single standardheater was used with water, as indicated. In other experiments, multipleheaters 22 were used. In yet other experiments, a single heater wasused, but the liquid used to activate the heater 22, was salt water. Thechart illustrates the substantial temperature increase due to the use ofthe ionized salt within the salt water. Throughout the course of theexperiment, the temperature was observably higher, and in some instancessubstantially higher, when salt water was the electrolyte initiating thereaction in the heaters 22. Moreover, a single heater, provided moretemperature rise in the reactor 20 than twice that amount of chemical(two standard heaters), relying only on water alone as the electrolyte.

Referring to FIG. 35, one may see that the insulation value of theinsulated container 26 has some effect. Nevertheless, in general, a morepronounced effect over the latter part of the subject time results fromthe addition of a second heater 22.

Referring to FIG. 36, in another experiment, the drop off over thesubject time period is more pronounced in the last half of the time.Meanwhile, the reactor temperature is maintained close to two hundreddegrees Fahrenheit for at least about 20 minutes, when two heaters areused.

Referring to FIG. 37, the volume of nitric oxide produced, cumulatively,over the operation of an apparatus 10 in accordance with the inventionprovided the illustrated results. In the chart, temperature wasmaintained for an extremely long period, considering that a therapysession may typically only require about 30 minutes of nitric oxidegeneration. The chart illustrates that the volumetric rate of nitricoxide generated was substantially constant, giving rise to asubstantially straight slope or line in the time period from about 16minutes to about 100 minutes. Meanwhile, although the measuredtemperature dropped during that time period from about two hundreddegrees Fahrenheit to just over one hundred degrees Fahrenheit, nitricoxide production did not drop off substantially throughout.Nevertheless, the graph illustrates an apparent decline eventually.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrative,and not restrictive. The scope of the invention is, therefore, indicatedby the appended claims, rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

1. An apparatus generating nitric oxide, the apparatus comprising: aheat source; a vessel containing reactants to form nitric oxide uponexposure to heat from the heat source; the reactants configured at leastone of solid tablets and a mixture of granules, positioned within thevessel and in thermal communication with the heat source to receive heattherefrom; the mixture further consisting substantially ofnon-deliquescent reactants forming nitric oxide in response to heat fromthe heat source; and an outlet conducting the nitric oxide away from theheat source to prohibit the nitric oxide from mixing and reacting withambient air after exiting the vessel.
 2. The apparatus of claim 1,wherein the mixture further comprises granules of reactants.
 3. Theapparatus of claim 1, wherein the granules are sized and the heat sourceis controlled to melt, yet avoid vaporizing, at least one of thereactants.
 4. The apparatus of claim 1, wherein the heat source iscontrolled to melt at least one of the reactants, and to avoidvaporizing any of the reactants.
 5. The apparatus of claim 1, whereinthe reactants consist substantially of: a metal oxide, anon-deliquescent nitrite compound; and a nitrate compound.
 6. Theapparatus of claim 1, wherein the non-deliquescent nitrite compoundcomprises sodium nitrite and the nitrate compound comprises potassiumnitrate.
 7. The apparatus of claim 1, wherein the metal oxide consistsessentially of chromic oxide, the nitrate compound consists essentiallyof potassium nitrate, and the nitrite consists essentially of sodiumnitrite.
 8. The apparatus of claim 1, wherein the pump is sized tomaintain substantially a vacuum in the vessel exclusive of the flow ofnitric oxide theretoward within the vessel.
 9. The apparatus of claim 1,wherein the pump is sized and operated to maintain a pressure in thevessel at a value of from about minus 14 and about minus 5 PSI gauge.10. The apparatus of claim 1, wherein the pump is sized and operated tomaintain a pressure in the vessel of less than about 5 PSI absolute. 11.A method of generating nitric oxide, the method comprising: providing amixture of reactants comprising a nitrate compound and a nitritecompound in a vessel; heating the reactants to initiate a reactiontherebetween generating nitric oxide gas; evacuating the nitric oxidegas away from the reactor in a closed conduit to inhibit further heatingthereof and to resist further reaction of the nitric oxide; cooling thenitric oxide; and delivering the nitric oxide at substantially ambientconditions to a user to provide a therapeutically safe concentration ofnitric oxide.
 12. The method of claim 11, further comprising granulatingthe reactants.
 13. The method of claim 11, further comprising sizing thegranules to melt and react, without vaporizing, at least one of thereactants.
 14. The method of claim 11, further comprising controllingthe heat source to control a rate of generation of the nitric oxide. 15.The method of claim 11, wherein the reactants consist essentially of: anon-deliquescent nitrite compound; a nitrate compound; and a metaloxide.
 16. The method of claim 15, wherein the non-deliquescent nitritecompound is sodium nitrite, the nitrate compound is potassium nitrate,and the metal oxide is chromic oxide.
 17. A method comprising: providinga mixture of reactants consisting essentially of potassium nitrate,sodium nitrite, and chromic oxide, the chromic oxide being calcined toremove substantially all water bonded thereto; placing the reactants ina vessel; substantially evacuating the vessel of moisture; heating thereactants to a temperature selected to initiate reaction thereof;generating nitric oxide; drawing the nitric oxide from the vessel atnegative gauge pressure to substantially preclude further heating andlimit further reaction of the nitric oxide; cooling the nitric oxide;mixing the nitric oxide with a diluent gas to form a mixture breathableby a subject; and delivering the breathable mixture, regulated tosubstantially ambient temperature and pressure to provide atherapeutically safe and effective concentration of nitric oxide to thesubject.